From the Department of Medicine, Division of Hematology, Mayo Clinic, Rochester, Minnesota
Author's disclosure of potential conflicts of interest is found at the end of this article.
Address reprint requests to Ayalew Tefferi, MD, Professor of Medicine and Hematology, Department of Medicine, Division of Hematology, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905; e-mail: tefferi.ayalew{at}mayo.edu
Overview: The BCR-ABL–negative classic myeloproliferative neoplasms include essential thrombocythemia, polycythemia vera, and primary myelofibrosis. Survival is relatively long in essential thrombocythemia and polycythemia vera (median greater than 15 years), but significantly less in primary myelofibrosis (median approximately 6 years). Similarly, leukemic transformations occur less frequently in essential thrombocythemia and polycythemia vera compared with primary myelofibrosis (estimated 10-year risks, 2%, 6%, and 20%, respectively). Unfortunately, current drug therapy does not result in improvement of these figures in terms of either survival or leukemia risk. Drugs are used to prevent thrombotic complications in high-risk patients with essential thrombocythemia or polycythemia vera and alleviate anemia, splenomegaly, or constitutional symptoms in primary myelofibrosis. In high-risk patients with primary myelofibrosis, both myeloablative and reduced intensity conditioning allogeneic stem cell transplantation have been used with some success. The recent discovery of JAK2 and MPL mutations in the majority of patients with polycythemia vera, essential thrombocythemia, and primary myelofibrosis has established JAK-STAT as a legitimate target for drug development; anti-JAK2 small molecule drugs are being evaluated in patients with primary myelofibrosis.
